It is our hypothesis that alcohol abuse leads to the depletion of polyunsaturated lipids from many tissues and leads to altered metabolism of eicosanoids. Such changes in the liver as well as in other organs and tissues may contribute to the pathological changes associated with alcoholism. Losses in arachidonic acid (20:4n6) and other n-6 fatty acids have been observed in our studies of alcohol exposed rat tissues as well as in the blood cells of alcoholics. This led to the question as to whether it was possible to replace these essential fatty acids by dietary manipulation. Animal studies have indicated that supplying the n-6 precursor, 18:3n6 in the diet can partially prevent the alcohol-induced loss of liver 20:4n6 when compared to diets high in 18:1n9 or long chain n-3 fatty acids. A clinical study of alcoholics during withdrawal has indicated that the composition of polyunsaturates is altered in a complex fashion in blood cells. Platelets exhibited a loss of a 20:4n6 species with increases in several non-essential phospholipid species in alcoholics at admittance. Most of these changes normalized after 4 weeks of withdrawal. In the erythrocyte, there was a loss of 18:2n6 and an increase in the non-essential species 18:0 and 18:1n9. None of the species that were abnormal at the beginning of alcohol withdrawal had normalized in the erythrocyte by 4 weeks. Arachidonyl species increased in PE while decreasing in PS. There was a generalized increase in phospholipid molecular species asymmetry in the erythrocyte membrane in alcoholics.